Senate Republicans suffered a dramatic failure early Friday in their bid to advance a scaled-back plan to overhaul the Affordable Care Act, throwing into question whether they can actually repeal the 2010 health law.

Their latest effort to redraw the ACA failed after Sen. John McCain’s decision to side with two other Republicans against President Trump and GOP leaders. The Arizona Republican, diagnosed with brain cancer last week, returned to Washington on Tuesday and delivered a stirring address calling for a bipartisan approach to overhauling the ACA, while criticizing the process that produced the current legislation.

It was a speech that laid the groundwork for Friday’s dramatic vote.

The vote was 49 to 51 — all 48 members of the Democratic caucus joined with McCain and Sens. Susan Collins (R-Maine) and Lisa Murkowski (R-Alaska) to block the legislation.

Senate Majority Leader Mitch McConnell (R-Ky.) had hoped to approve the new, narrower rewrite of the health law at some point Friday, after facing dozens of amendments from Democrats. But the GOP defections left McConnell without a clear path forward.

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“Our only regret is that we didn’t achieve what we hoped to accomplish,” McConnell said after the failed vote. In a dejected tone, he pulled the entire legislation from consideration and set up votes on nominations that will begin Monday.

“It is time to move on,” McConnell said, culminating a nearly 75-minute set of roll calls. In a last-minute rescue bid, Vice President Pence — there to be the tie-breaking vote if needed — stood at McCain’s desk for 21 minutes cajoling the senator to no avail.

McCain and Pence then walked to the Republican cloak room to confer in private and later to the lobby off the Senate chamber. When McCain returned — without Pence — he stopped in the well of the chamber, cast his “no” vote — sparking stunned gasps and some applause — and returned to his seat.

McConnell and his leadership deputies stood watching, grim-faced and despondent.

“We must now return to the correct way of legislating and send the bill back to committee, hold hearings, receive input from both sides of aisle, heed the recommendations of nation’s governors, and produce a bill that finally delivers affordable health care for the American people,” McCain said in a statement explaining his vote. “We must do the hard work our citizens expect of us and deserve.”

Some senators in both parties said they hope the two sides can begin talks on shoring up the current health-care system, a debate that is expected to be handled by Senate committees overseeing budget, tax and health-care policy.

“Maybe this had to happen to actually begin to have a conversation,” said Sen. Bill Cassidy (R-La.), who had tried brokering a bipartisan deal in recent weeks.

The bill’s fate began to collapse Thursday as McCain sought an iron-clad guarantee from Speaker Paul D. Ryan (R-Wis.) that, if the Senate approved this latest proposal, the House would not move to quickly approve the bill in its current form and instead engage in a broad House-Senate negotiation for a wider rollback of the law. Ryan issued a statement intended to assuage the concerns of McCain and two others, Sens. Lindsey O. Graham (R-S.C.) and Ron Johnson (R-Wis.), but the 2008 presidential nominee deemed the speaker’s statement as insufficient.

The standoff between the two chambers highlighted the extent to which Republicans have still not reached a consensus on how to rewrite President Barack Obama’s 2010 health-care law, and the degree to which Republicans are repeating many of the same back-room maneuvers that Democrats used seven years ago to approve the ACA.

McConnell’s draft rattled moderates like Collins and Murkowski and Republicans who wanted a more robust uprooting of the existing law.

“I’m not going to tell people back in South Carolina that this product actually replaces Obamacare, because it does not, it is a fraud,” Graham said at a Thursday evening news conference with McCain and Johnson at his side.

And while GOP senators insisted the bill they were considering would not make it into law, if enacted it would have made sweeping changes to health coverage as well as medical treatment in the United States.

It would have eliminated enforcement of the ACA’s requirement that Americans obtain insurance or pay a tax penalty, and suspended for eight years enforcing the mandate that companies employing 50 or more workers provide coverage.

The measure also would have eliminated funding for preventive health care provided under the 2010 law and prohibited Medicaid beneficiaries from being reimbursed for Planned Parenthood services for one year. Instead, the bill aimed to steer funding to community health centers. It would have ended a 2.3 percent tax on medical device manufacturers for three years.

And it would have empowered federal officials under an existing waiver program to give states wide latitude in how they allocate their Medicaid funding, potentially pooling that money with other programs such as one that helps lower-income Americans buy private insurance. It also would have increased the limit on contributions to tax-exempt health savings accounts for three years.

Translating their pledge to repeal what they derisively call Obamacare into a law has proved embarrassingly difficult for Republicans. First, the House took an extra six weeks to pass its version of the bill in early May. Most Republicans agreed that the measure was flawed — Trump later called it “mean” for how it would deny insurance to 23 million people — and hoped that the Senate would craft a better bill.

But McConnell’s closed-door negotiations ended in gridlock, leaving him to pull together this “skinny” repeal of the ACA, just to keep alive the possibility of negotiations with the House to come up with a different plan later this summer.

Many conservatives in both chambers objected to the measure because they said it wouldn’t go far enough in repealing the ACA.

For instance, the expansion of federal funding to use Medicaid to provide insurance to about 14 million Americans was left intact, a major victory for a half-dozen Senate Republicans from states that accepted the additional money. Governors, under the new Senate proposal, would have more leeway in how they can spend Medicaid funding overall.

Major insurers warned that the proposal could destabilize the individual insurance market. Blue Cross Blue Shield Association criticized it on Wednesday, and on Thursday the industry’s largest trade group suggested it was unacceptable.

“We would oppose an approach that eliminates the individual coverage requirement, does not offer continuous coverage solutions, and does not include measures to immediately stabilize the individual market,” America’s Health Insurance Plans wrote in a letter to Senate leaders.

Senate Republicans, however, framed the bill as just a vehicle to keep alive their ACA repeal efforts.

“My sense is people aren’t so much focused on the substance as they are this being the lifeline to get to a conference and expanding the bill,” said Sen. Bob Corker (Tenn.).

Before Ryan issued his statement, the prospect of an immediate up-or-down vote in the House raised alarms in the Senate. House Republican leaders instructed their members not to leave town for their month-long summer recess just yet.

Key House conservatives said they would not back a skinny repeal in its current form. Rep. Mark Meadows (R-N.C.), chairman of the House Freedom Caucus, said that he wouldn’t vote for such a measure and that he didn’t think other conservatives would, either.

Speaking on the Senate floor Thursday, McConnell emphasized that the votes this week would not reverse the ACA even if they culminate in the passage of a bill.

“One phase of that process will end when the Senate concludes voting this week, but it will not signal the end of our work. Not yet,” he said.

In an effort to muster enough votes for a narrow bill, GOP leaders suggested that even some proposals that have died in the Senate could resurface once senators entered negotiations with the House. And some members tried to add a few more provisions to the skinny bill, using their leverage to try to strengthen their negotiating positions in conference.

While McConnell has led the negotiations over health-care legislation for weeks, Trump sought to drum up support by pressing wavering Republicans.

Interior Secretary Ryan Zinke called Murkowski and Sen. Dan Sullivan (R-Alaska) separately Wednesday to warn them that the administration may change its position on several issues, according to people briefed on the conversations, given Murkowski’s vote against proceeding with health-care legislation this week.

Since Trump took office, Interior has indicated that it is open to constructing a road through the Izembek National Wildlife Refuge and drilling in the Arctic National Wildlife Refuge while expanding energy exploration elsewhere in Alaska. But now these policy shifts may be in jeopardy.

Speaking to reporters Thursday, Sullivan said the Trump administration has been cooperative on Alaska issues with Murkowski, who chairs the Senate Energy and Natural Resources Committee.

“From my perspective, the sooner we can get back to that kind of cooperation between the administration and the chairman of the ENR Committee, the better for Alaska and the better for the country,” he said. Sullivan said he is not telling Murkowski how to respond.

The Alaska Dispatch News first reported the calls; Interior officials did not respond to a request for comment.